Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES)

McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Trapnell BC · 2011 · New England Journal of Medicine · Atlas ID MCC2011

What this study shows

A landmark placebo-controlled RCT (n=89) - the first to show that rapamycin (sirolimus) benefits a human lung disease. In LAM, lung function normally declines relentlessly; sirolimus STOPPED that decline while patients took it (and it resumed after stopping). Randomised human evidence that mTOR inhibition can suspend progression of this disease; the benefit did not persist after withdrawal.

Abstract

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Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period.

Read the full abstract on PubMed →

At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Humans, RCT (n=89, women with LAM)
Journal	New England Journal of Medicine
Year	2011
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1056/NEJMoa1100391 · PMID 21410393 · Free full text (PMC3118601)

Extracted findings

Intervention	Sirolimus (rapamycin)
Target	mTOR
Model	Human – RCT (MILES, n=89, women with LAM)
Effect	Sirolimus stabilized lung function (FEV1) in lymphangioleiomyomatosis during treatment
Dose	Oral sirolimus, initial 2 mg/day titrated to trough 5-15 ng/ml; 12-month double-blind treatment + 12-month observation off-drug; 1:1 vs placebo (MILES).
Sample size	111 consented, 89 randomized (43 placebo / 46 sirolimus); women with LAM, FEV1 <=70% predicted.
Effect size	Primary outcome FEV1 slope (mL/month): sirolimus stabilized lung function during treatment while placebo declined; benefit waned after stopping the drug.
Limitations	Interim analysis delayed by site/contracting issues; other health-symptom measures not significantly different; benefit tied to continued dosing.

In the Atlas

Cite this paper

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McCormack, F. X., Inoue, Y., Moss, J., Singer, L. G., Strange, C., & Trapnell, B. C. (2011). Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES). New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1100391

@article{MCC2011,
  author       = {McCormack, F. X. and Inoue, Y. and Moss, J. and Singer, L. G. and Strange, C. and Trapnell, B. C.},
  title        = {{Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES)}},
  journal      = {New England Journal of Medicine},
  year         = {2011},
  doi          = {10.1056/NEJMoa1100391},
  note         = {PMID: 21410393},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record MCC2011) [Data set]. https://mtor-atlas.org/study/MCC2011/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MCC2011,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MCC2011},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MCC2011/},
  doi          = {10.5281/zenodo.22059963}
}